Whole genome microarray analysis of gene expression in Prader-Willi syndrome
Whole genome microarray analysis of gene expression in Prader-Willi syndrome
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DOI：
10.1002/ajmg.a.31606
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发表时间：
2007-03-01
影响因子：
2
通讯作者：
Butler, Merlin G.
中科院分区：
文献类型：
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作者：
Bittel, Douglas C.;Kibiryeva, Nataliya;Butler, Merlin G.
Prader-Willi综合征（PWS）是由15 q11-q13区域的父系表达基因的功能丧失引起的，并且缺乏关于转录组变异的数据。为了使用全基因组微阵列分析基因表达，进一步表征这种典型肥胖综合征的遗传改变，使用从PWS男性受试者（4例15 q11-q13缺失，3例UPD）和3例年龄和认知匹配的非综合征对照男性的淋巴母细胞中分离的RNA进行微阵列和定量RT-PCR分析。在微阵列中检测的超过47，000个探针中，23，383个是可检测的，323个相对于比较细胞在PWS淋巴母细胞样细胞中具有显著不同的表达，其中14个与神经发育和功能相关。正如预期的那样，没有证据表明来自15 q11-q13区域的父系表达基因（例如，SNRPN）在PWS细胞中。5-羟色胺受体基因表达的改变（例如，HTR 2B）和参与饮食行为和肥胖的基因（ADIPOR 2、MC 2 R、HCRT、OXTR）。在PWS受试者中表达减少的其他感兴趣的基因包括星星（类固醇合成的关键调节因子）和SAG（使G蛋白偶联受体脱敏的抑制蛋白家族成员）。SAG、OXTR、星星、HCRT和HTR 2 B的定量RT-PCR使用从其淋巴母细胞样细胞和来自PWS个体和对照受试者的可用脑组织（额叶皮质）分离的RNA，并归一化为GAPD基因表达水平，验证了我们的微阵列基因表达数据。我们的分析确定了以前未被重视的基因表达变化，这可能有助于PWS的临床表现。(c)2007 Wiley-Liss，Inc.
Prader-Willi syndrome (PWS) is caused by loss of function of paternally expressed genes in the 15q11-q13 region and a paucity of data exists on transcriptome variation. To further characterize genetic alterations in this classic obesity syndrome using whole genome microarrays to analyze gene expression, microarray and quantitative RT-PCR analysis were performed using RNA isolated from lymphoblastoid cells from PWS male subjects (four with 15q11-q13 deletion and three with UPD) and three age and cognition matched nonsyndromic comparison males. Of more than 47,000 probes examined in the microarray, 23,383 were detectable and 323 had significantly different expression in the PWS lymphoblastoid cells relative to comparison cells, 14 of which were related to neurodevelopment and function. As expected, there was no evidence of expression of paternally expressed genes from the 15q11-q13 region (e.g., SNRPN) in the PWS cells. Alterations in expression of serotonin receptor genes (e.g., HTR2B) and genes involved in eating behavior and obesity (ADIPOR2, MC2R, HCRT, OXTR) were noted. Other genes of interest with reduced expression in PWS subjects included STAR (a key regulator of steroid synthesis) and SAG (an arrestin family member which desensitizes G-protein-coupled receptors). Quantitative RT-PCR for SAG, OXTR, STAR, HCRT, and HTR2B using RNA isolated from their lymphoblastoid cells and available brain tissue (frontal cortex) from separate individuals with PWS and control subjects and normalized to GAPD gene expression levels validated our microarray gene expression data. Our analysis identified previously unappreciated changes in gene expression which may contribute to the clinical manifestations seen in PWS. (c) 2007 Wiley-Liss, Inc.